HPV urine test could screen for cervical cancer

"A simple urine test which can detect the human papilloma virus (HPV) could offer women a much less invasive alternative to [current] cervical cancer screening," The Independent reports.

Research found urine-based testing for HPV DNA showed signs it might be accurate enough to provide a viable screening method, given further research and development.

The papers report on a review of 14 diverse studies involving 1,443 women. All of the studies looked at the accuracy of using a self-administered urine test designed to detect HPV DNA. HPV is a group of viruses, some of which can cause cervical cancer in women.

The advantage of such a self-administered urine test is it may improve uptake of cervical screening. As the researchers speculate, some women may be put off by current screening methods (which involve using a tool to painlessly remove a sample of cells from the cervix) as they may find it embarrassing and time consuming.

This drop-off in women who attend screening, especially younger women, is of concern as around 3,000 cases of cervical cancer are diagnosed each year in the UK.

The review findings are promising, but need to be followed up by further investigation and the standardisation of the urine testing method so the potential of using these tests as a screening tool can be assessed.

Where did the story come from?

The study was carried out by researchers from The London School of Medicine and Dentistry (England), Clinical Biostatistics Unit, Hospital Ramon y Cajal (Spain), and CIBER Epidemiologia y Salud Publica (Spain).

Generally, the media reported the story accurately but tended to focus on the new urine test as a replacement for the current smear test.

An alternative angle, and perhaps a more likely scenario, would be that the test would be used in tandem with the current smear test, providing an additional option for some women and adding more choice.

In any case, an initial "positive" urine sample result would more than likely be followed up by current cervical screening methods to confirm or disprove the preliminary result.

What kind of research was this?

This was a systematic review and meta-analysis to determine the accuracy of testing for HPV DNA in urine to detect cervical HPV in sexually active women.

HPV is one of the most common sexually transmitted infections. Infection with specific strains of HPV has been associated with the development of cervical cancer, a preventable and treatable disease.

Cervical screening has traditionally relied on samples of cervical cells taken from the cervix (neck of the womb/uterus) using a spatula under direct vision by a health professional.

Despite screening, cervical cancer is still the most common malignancy in women aged under 35, the publication states. It says there has been a downward trend in coverage of screening in the under 35s, which may partly be because the current screening using cervical cytology sampling is invasive, time consuming and requires a clinician.

Less invasive, more convenient ways of screening are therefore desirable, such as a urine test. According to the authors, this has led to the rigorous evaluation of HPV DNA testing of cervical samples as a potential method of primary screening, and HPV testing is now set to replace cytology in several national screening programmes.

What did the research involve?

The review team searched for studies assessing the accuracy of urine HPV DNA tests in sexually active women. Data was collected relating to patient characteristics, study context, risk of bias, and test accuracy.

The researchers pooled the results of the different studies to estimate the overall test accuracy to detect HPV DNA in general, but also to detect HPV subtypes linked to a higher risk of cervical cancer.

To find relevant literature, the team searched several electronic databases from study inception to December 2013, then manually searched reference lists of these articles for further relevant articles and contacted topic experts. No language restrictions were placed on the literature search.

Studies were included where the detection of HPV DNA in urine was compared with its detection in the cervix in any sexually active woman concerned about HPV infection or the development of cervical cancer. Studies were excluded if a different or no reference standard was used, or if they were of a case-control design.

What were the basic results?

The search identified 16 relevant research papers based on 14 studies involving 1,443 women in total. The main results were:

Urine detection of any HPV had a pooled sensitivity (the proportion of the urine tests correctly showing HPV was present) of 87% (95% confidence interval [CI], 78% to 92%) and specificity (the proportion of the urine tests correctly showing HPV was absent) of 94% (95% CI, 82% to 98%).

Urine detection of high-risk HPV had a pooled sensitivity of 77% (95% CI, 8% to 84%) and specificity of 88% (95% CI, 58% to 97%).

Urine detection of HPV 16 and 18 subtypes – some of the subtypes most likely to cause cancer – had a pooled sensitivity of 73% (95% CI, 56% to 86%) and specificity of 98% (95% CI, 91% to 100%).

Most HPV urine tested for HPV DNA in first void volumes – this is a sample from the first urine passed in the morning after you wake up. Other studies used midstream urination samples or random urine samples from any time of day.

Meta-analysis showed an increase in sensitivity when urine samples were collected as first void compared with random or midstream.

How did the researchers interpret the results?

The authors commented that, "Our review demonstrates the accuracy of detection of HPV in urine for the presence of cervical HPV. When cervical testing for HPV is sought, urine-based testing should be an acceptable alternative to increase coverage for subgroups that are hard to reach.

"However, results must be interpreted with caution owing to variation between individual studies for participant characteristics, lack of standardised methods of urine testing, and the surrogate nature of cervical HPV for cervical disease."

Conclusion

This systematic review and meta-analysis indicates that urine tests for detecting HPV DNA might be feasible for screening women for cervical cancer based on an evidence base of 14 diverse studies involving 1,443 women.

While it is feasible this type of test might be useful for screening, there were many limitations in the evidence base reviewed. This means its effectiveness as a screening tool is still up for debate and is unproven.

Issues include:

the large variation between individual studies for participant characteristics

the large variation in estimates of test sensitivity and specificity between individual studies

This ultimately meant a relatively diverse test of screening tests, participants and results were lumped together to give a summary result of test accuracy. This means the pooled result may not actually be a good representation of the underlying studies as they are not a uniform group.

The BMJ editorial summed up how future research could address many of these limitations. "If serious consideration is to be given to using urine HPV testing in cervical screening programmes, then further evaluation is essential, including an adequately powered, high-quality prospective study comparing urine testing with vaginal self-sampling and reporting the detection of high grade CIN [pre-cancer] as the primary endpoint.

"Participants could do both tests without the quality of one sample being reduced by the other. The study could be performed in women attending for routine screening, with urine and vaginal samples collected before the 'gold standard' cervical sample. Ideally, samples would be obtained using standardised protocols and tested using a single validated HPV test."

On the flip side, a strength of this study was the search protocol of systematic review. This seems robust and appeared to have a good chance of identifying all the relevant literature.

We agree with the study authors and the BMJ editorial that these findings are promising, but need to be followed up by further investigation and standardisation of urine testing used in this way.

The benefits of such a test, if successful, are potentially large. For example, it may increase screening rates that ultimately save lives through the early detection of cancer. Women may be more comfortable, and find it more convenient, to test for HPV using a self-administered urine test rather than the current smear test, which requires a visit to a medical establishment with all of its attendant connotations (such as the need to make an appointment and potential emotional effects, for example).

However, because the urine test has not been proven to work as a screening tool, it is not available routinely on the NHS. In the meantime, there are three main ways to reduce the risk of cervical cancer: vaccination, current cervical cancer screening (the smear test), and safe sex using a condom.